Platform trials for anaesthesia and perioperative medicine: a narrative review.

Large randomised trials provide the most reliable evidence of effectiveness of new treatments in clinical practice. However, the time and resources required to complete such trials can be daunting. An overarching clinical trial platform focused on a single condition or type of surgery, aiming to compare several treatments, with an option to stop any or add in new treatment options, can provide greater efficiency. This has the potential to accelerate knowledge acquisition and identify effective, ineffective, or harmful treatments faster. The master protocol of the platform defines the study population(s) and standardised procedures. Ineffective or harmful treatments can be discarded or study drug dose modified during the life cycle of the trial. Other adaptive elements that can be modified include eligibility criteria, required sample size for any comparison(s), randomisation assignment ratio, and the addition of other promising treatment options. There are excellent opportunities for anaesthetists to establish platform trials in perioperative medicine. Platform trials are highly efficient, with the potential to provide quicker answers to important clinical questions that lead to improved patient care.

Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. ß-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality. Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support. Design, Setting, and Participants: An open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 µg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm. Intervention: Sixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion. Main Outcomes and Measures: The primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group. Results: The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, -0.49 to 2.0]; P = .24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, -4.4% to 27.8%]; P = .16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, -1.7% to 31.6%]; P = .08). There were no differences in the number of patients having at least one adverse event. Conclusion and Relevance: Among patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919.

On the horns of a dilemma: choosing total intravenous anaesthesia or volatile anaesthesia.

There are two established techniques of delivering general anaesthesia: propofol-based total intravenous anaesthesia (TIVA) and volatile agent-based inhaled anaesthesia. Both techniques are offered as standard of care and have an established safety track record lasting more than 30 years. However, it is not currently known whether the choice of anaesthetic technique results in a fundamentally different patient experience or affects early, intermediate-term, and longer-term postoperative outcomes. This editorial comments on a recently published study that suggests that inhaled volatile anaesthesia might be associated with fewer postoperative surgical complications than propofol-based TIVA for patients undergoing colorectal cancer surgery. We consider the strengths and limitations of the study, place these findings in the context of the broader evidence, and discuss how the current controversies regarding anaesthetic technique can be resolved, thereby helping to bring precision medicine into the modern practice of perioperative care.

Clinical effectiveness and safety of spinal anaesthesia compared with general anaesthesia in patients undergoing hip fracture surgery using a consensus-based core outcome set and patient-and public-informed outcomes: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: We conducted a systematic review and meta-analysis of contemporary RCTs to determine the clinical effectiveness of spinal vs general anaesthesia (SA vs GA) in patients undergoing hip fracture surgery using a consensus-based core outcome set, and outcomes defined as important by patient and public involvement (PPI) initiatives. METHODS: RCTs comparing any of the core outcomes (mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1 postoperatively, and pain) or PPI-defined outcomes (return to preoperative residence, quality of life, and mobility status) between SA and GA were identified from MEDLINE, Embase, Cochrane Library, and Web of Science (2000 to February 2022). Pooled relative risks (RRs) and mean differences (95% confidence intervals [CIs]) were estimated. RESULTS: There was no significant difference in the risk of delirium comparing SA vs GA (RR=1.07; 95% CI, 0.90-1.29). Comparing SA vs GA, the RR for mortality was 0.56 (95% CI, 0.22-1.44) in-hospital, 1.07 (95% CI, 0.52-2.23) at 30 days, and 1.08 (95% CI, 0.55-2.12) at 90 days. Spinal anaesthesia reduced the risk of acute kidney injury compared with GA: RR=0.59 (95% CI, 0.39-0.89). There were no significant differences in the risk of other outcomes. Few studies reported PPI-defined outcomes, with most studies reporting on one to three core outcomes. CONCLUSIONS: Except for acute kidney injury, there were no differences between SA and GA in hip fracture surgery when using a consensus-based core outcome set and patient and public involvement-defined outcomes. Most studies reported limited outcomes from the core outcome set, and few reported outcomes important to patients, which should be considered when designing future RCTs. PROSPERO REGISTRATION: CRD42021275206.

Effect of Regional vs General Anesthesia on Incidence of Postoperative Delirium in Older Patients Undergoing Hip Fracture Surgery: The RAGA Randomized Trial.

Importance: In adults undergoing hip fracture surgery, regional anesthesia may reduce postoperative delirium, but there is uncertainty about its effectiveness. Objective: To investigate, in older adults undergoing surgical repair for hip fracture, the effects of regional anesthesia on the incidence of postoperative delirium compared with general anesthesia. Design, Setting, and Participants: A randomized, allocation-concealed, open-label, multicenter clinical trial of 950 patients, aged 65 years and older, with or without preexisting dementia, and a fragility hip fracture requiring surgical repair from 9 university teaching hospitals in Southeastern China. Participants were enrolled between October 2014 and September 2018; 30-day follow-up ended November 2018. Interventions: Patients were randomized to receive either regional anesthesia (spinal, epidural, or both techniques combined with no sedation; n = 476) or general anesthesia (intravenous, inhalational, or combined anesthetic agents; n = 474). Main Outcomes and Measures: Primary outcome was incidence of delirium during the first 7 postoperative days. Secondary outcomes analyzed in this article include delirium severity, duration, and subtype; postoperative pain score; length of hospitalization; 30-day all-cause mortality; and complications. Results: Among 950 randomized patients (mean age, 76.5 years; 247 [26.8%] male), 941 were evaluable for the primary outcome (6 canceled surgery and 3 withdrew consent). Postoperative delirium occurred in 29 (6.2%) in the regional anesthesia group vs 24 (5.1%) in the general anesthesia group (unadjusted risk difference [RD], 1.1%; 95% CI, -1.7% to 3.8%; P = .48; unadjusted relative risk [RR], 1.2 [95% CI, 0.7 to 2.0]; P = .57]). Mean severity score of delirium was 23.0 vs 24.1, respectively (unadjusted difference, -1.1; 95% CI, -4.6 to 3.1). A single delirium episode occurred in 16 (3.4%) vs 10 (2.1%) (unadjusted RD, 1.1%; 95% CI, -1.7% to 3.9%; RR, 1.6 [95% CI, 0.7 to 3.5]). Hypoactive subtype in 11 (37.9%) vs 5 (20.8%) (RD, 11.5; 95% CI, -11.0% to 35.7%; RR, 2.2 [95% CI, 0.8 to 6.3]). Median worst pain score was 0 (IQR, 0 to 20) vs 0 (IQR, 0 to 10) (difference 0; 95% CI, 0 to 0). Median length of hospitalization was 7 days (IQR, 5 to 10) vs 7 days (IQR, 6 to 10) (difference 0; 95% CI, 0 to 0). Death occurred in 8 (1.7%) vs 4 (0.9%) (unadjusted RD, -0.8%; 95% CI, -2.2% to 0.7%; RR, 2.0 [95% CI, 0.6 to 6.5]). Adverse events were reported in 106 episodes in the regional anesthesia group and 102 in the general anesthesia group; the most frequently reported adverse events were nausea and vomiting (47 [44.3%] vs 34 [33.3%]) and postoperative hypotension (13 [12.3%] vs 10 [9.8%]). Conclusions and Relevance: In patients aged 65 years and older undergoing hip fracture surgery, regional anesthesia without sedation did not significantly reduce the incidence of postoperative delirium compared with general anesthesia. Trial Registration: ClinicalTrials.gov Identifier: NCT02213380.

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective: To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants: A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions: Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures: The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results: The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration: isrctn.org Identifier: ISRCTN16912075.

Education, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

For this 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

[Cardiac arrest under special circumstances]. / Kreislaufstillstand unter besonderen Umständen: Leitlinien des European Resuscitation Council 2021.

These guidelines of the European Resuscitation Council (ERC) Cardiac Arrest under Special Circumstances are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidelines on the modifications required for basic and advanced life support for the prevention and treatment of cardiac arrest under special circumstances; in particular, specific causes (hypoxia, trauma, anaphylaxis, sepsis, hypo-/hyperkalaemia and other electrolyte disorders, hypothermia, avalanche, hyperthermia and malignant hyperthermia, pulmonary embolism, coronary thrombosis, cardiac tamponade, tension pneumothorax, toxic agents), specific settings (operating room, cardiac surgery, cardiac catheterization laboratory, dialysis unit, dental clinics, transportation [in-flight, cruise ships], sport, drowning, mass casualty incidents), and specific patient groups (asthma and chronic obstructive pulmonary disease, neurological disease, morbid obesity, pregnancy).

[Education for resuscitation]. / Lehre in der Reanimation: Leitlinien des European Resuscitation Council 2021.

These European Resuscitation Council education guidelines are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. This section provides guidance to citizens and healthcare professionals with regard to teaching and learning the knowledge, skills and attitudes of resuscitation with the ultimate aim of improving patient survival after cardiac arrest.

The risks associated with tourniquet use in lower limb trauma surgery: a systematic review and meta-analysis.

PURPOSE: Tourniquet use in lower limb fracture surgery may reduce intra-operative bleeding, improve surgical field of view and reduce length of procedure. However, tourniquets may result in pain and the production of harmful metabolites cause complications or affect functional outcomes. This systematic review aimed to compare outcomes following lower limb fracture surgery performed with or without tourniquet. METHODS: We searched databases for RCTs comparing lower limb fracture surgery performed with versus without tourniquet reporting on outcomes pain, physical function, health-related quality of life, complications, cognitive function, blood loss, length of stay, length of procedure, swelling, time to union, surgical field of view, volume of anaesthetic agent, biochemical markers of inflammation and injury, and electrolyte and acid-base balance. Random-effects meta-analysis was performed. PROSPERO ID CRD42020209310. RESULTS: Six RCTs enabled inclusion of 552 procedures. Pooled analysis demonstrated that tourniquet use reduced length of procedure by 6 minutes (95% CI -10.12 to -1.87; p < 0.010). We were unable to exclude increased harms from tourniquet use. Pooled analysis showed post-operative pain score was higher in tourniquet group by 12.88 on 100-point scale (95% CI -1.25-27.02; p = 0.070). Risk differences for wound infection, deep venous thrombosis and re-operation were 0.06 (95% CI -0.00-0.12; p = 0.070), 0.05 (95% CI -0.02-0.11; p = 0.150) and 0.03 (95% CI -0.03-0.09; p = 0.340). CONCLUSION: Tourniquet use was associated with a reduced length of procedure. It is possible that tourniquets also increase incidence of important complications, but the data are too sparse to draw firm conclusions. Methodological weaknesses of the included RCTs prevent any solid conclusions being drawn for outcomes investigated. Further studies are required to address these limitations.

A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.

BACKGROUND: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α. OBJECTIVE: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy. DESIGN: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study. SETTING: Eight secondary care centres, the United Kingdom between April 2015 and June 2017. PATIENTS: Thirty-three patients undergoing elective transthoracic oesophagectomy. INTERVENTIONS: Patients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study. MAIN OUTCOME MEASUREMENTS: Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models. RESULTS: The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (-0.23, 0.39) in the placebo and 0.00 (-0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms. CONCLUSION: Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation. TRIAL REGISTRATION: clinicaltrials.gov: NCT02221037.

A Snapshot of Compliance with the Sepsis Six Care Bundle in Two Acute Hospitals in the West Midlands, UK.

BACKGROUND: The sepsis six care bundle has been adopted by hospitals in England and Wales for the management of patients with sepsis, with the aim of increasing survival when all elements of the bundle are achieved. AIM: To assess compliance with the Sepsis Six Care Bundle in two acute NHS hospitals in the West Midlands. MATERIALS AND METHODS: Adults admitted to hospital over a 24-hour period were screened for sepsis. Sepsis was identified using the Systemic Inflammatory Response (SIRS) criteria and the quick sequential organ failure assessment (qSOFA) score. Adherence to the Sepsis Six Care Bundle was assessed. RESULTS: 249 patients were screened and 24 patients were identified as having sepsis (9.6%). One patient received all six elements of the bundle. Compliance was highest for giving intravenous fluids (58.3%) and antibiotics (58.3%), and lowest for measuring urine output (16.7%). CONCLUSIONS: Further research is needed to establish the reasons for low compliance. HOW TO CITE THIS ARTICLE: Frankling C, Patel J, Sharif B, Melody T, Yeung J, Gao F, et al. A Snapshot of Compliance with the Sepsis Six Care Bundle in Two Acute Hospitals in the West Midlands, UK. Indian J Crit Care Med 2019;23(7):310-315.

Mechanical CPR: Who? When? How?

In cardiac arrest, high quality cardiopulmonary resuscitation (CPR) is a key determinant of patient survival. However, delivery of effective chest compressions is often inconsistent, subject to fatigue and practically challenging.Mechanical CPR devices provide an automated way to deliver high-quality CPR. However, large randomised controlled trials of the routine use of mechanical devices in the out-of-hospital setting have found no evidence of improved patient outcome in patients treated with mechanical CPR, compared with manual CPR. The limited data on use during in-hospital cardiac arrest provides preliminary data supporting use of mechanical devices, but this needs to be robustly tested in randomised controlled trials.In situations where high-quality manual chest compressions cannot be safely delivered, the use of a mechanical device may be a reasonable clinical approach. Examples of such situations include ambulance transportation, primary percutaneous coronary intervention, as a bridge to extracorporeal CPR and to facilitate uncontrolled organ donation after circulatory death.The precise time point during a cardiac arrest at which to deploy a mechanical device is uncertain, particularly in patients presenting in a shockable rhythm. The deployment process requires interruptions in chest compression, which may be harmful if the pause is prolonged. It is recommended that use of mechanical devices should occur only in systems where quality assurance mechanisms are in place to monitor and manage pauses associated with deployment.In summary, mechanical CPR devices may provide a useful adjunct to standard treatment in specific situations, but current evidence does not support their routine use.

The implementation of cardiac arrest treatment recommendations in English acute NHS trusts: a national survey.

PURPOSE OF THE STUDY: There are approximately 35 000 in-hospital cardiac arrests in the UK each year. Successful resuscitation requires integration of the medical science, training and education of clinicians and implementation of best practice in the clinical setting. In 2015, the International Liaison Committee on Resuscitation (ILCOR) published its latest resuscitation treatment recommendations. It is currently unknown the extent to which these treatment recommendations have been successfully implemented in practice in English NHS acute hospital trusts. METHODS: We conducted an electronic survey of English acute NHS trusts to assess the implementation of key ILCOR resuscitation treatment recommendations in relation to in-hospital cardiac arrest practice at English NHS acute hospital trusts. RESULTS: Of 137 eligible trusts, 73 responded to the survey (response rate 53.3%). The survey identified significant variation in the implementation of ILCOR recommendations. In particular, the use of waveform capnography (n=33, 45.2%) and ultrasound (n=29, 39.7%) was often reported to be available only in specialist areas. Post-resuscitation debriefing occurs following every in-hospital cardiac arrest in few trusts (5.5%, n=4), despite a strong ILCOR recommendation. In contrast, participation in a range of quality improvement strategies such as the National Cardiac Arrest Audit (90.4%, n=66) and resuscitation equipment provision/audit (91.8%, n=67) were high. Financial restrictions were identified by 65.8% (n=48) as the main barrier to guideline implementation. CONCLUSION: Our survey found that ILCOR treatment recommendations had not been fully implemented in most English NHS acute hospital trusts. Further work is required to better understand barriers to implementation.

Paravertebral block versus thoracic epidural for patients undergoing thoracotomy.

BACKGROUND: Operations on structures in the chest (usually the lungs) involve cutting between the ribs (thoracotomy). Severe post-thoracotomy pain can result from pleural (lung lining) and muscular damage, costovertebral joint (ribcage) disruption and intercostal nerve (nerves that run along the ribs) damage during surgery. Poor pain relief after surgery can impede recovery and increase the risks of developing complications such as lung collapse, chest infections and blood clots due to ineffective breathing and clearing of secretions. Effective management of acute pain following thoracotomy may prevent these complications and reduce the likelihood of developing chronic pain. A multi-modal approach to analgesia is widely employed by thoracic anaesthetists using a combination of regional anaesthetic blockade and systemic analgesia, with both non-opioid and opioid medications and local anaesthesia blockade.There is some evidence that blocking the nerves as they emerge from the spinal column (paravertebral block, PVB) may be associated with a lower risk of major complications in thoracic surgery but the majority of thoracic anaesthetists still prefer to use a thoracic epidural blockade (TEB) as analgesia for their patients undergoing thoracotomy. In order to bring about a change in practice, anaesthetists need a review that evaluates the risk of all major complications associated with thoracic epidural and paravertebral block in thoracotomy. OBJECTIVES: To compare the two regional techniques of TEB and PVB in adults undergoing elective thoracotomy with respect to:1. analgesic efficacy;2. the incidence of major complications (including mortality);3. the incidence of minor complications;4. length of hospital stay;5. cost effectiveness. SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 9); MEDLINE via Ovid (1966 to 16 October 2013); EMBASE via Ovid (1980 to 16 October 2013); CINAHL via EBSCO host (1982 to 16 October 2013); and reference lists of retrieved studies. We handsearched the Journal of Cardiothoracic Surgery and Journal of Cardiothoracic and Vascular Anesthesia (16 October 2013). We reran the search on 31st January 2015. We found one additional study which is awaiting classification and will be addressed when we update the review. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing PVB with TEB in thoracotomy, including upper gastrointestinal surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors (JY and SG) independently assessed the studies for inclusion and then extracted data as eligible for inclusion in qualitative and quantitative synthesis (meta-analysis). MAIN RESULTS: We included 14 studies with a total of 698 participants undergoing thoracotomy. There are two studies awaiting classification. The studies demonstrated high heterogeneity in insertion and use of both regional techniques, reflecting real-world differences in the anaesthesia techniques. Overall, the included studies have a moderate to high potential for bias, lacking details of randomization, group allocation concealment or arrangements to blind participants or outcome assessors. There was low to very low-quality evidence that showed no significant difference in 30-day mortality (2 studies, 125 participants. risk ratio (RR) 1.28, 95% confidence interval (CI) 0.39 to 4.23, P value = 0.68) and major complications (cardiovascular: 2 studies, 114 participants. Hypotension RR 0.30, 95% CI 0.01 to 6.62, P value = 0.45; arrhythmias RR 0.36, 95% CI 0.04 to 3.29, P value = 0.36, myocardial infarction RR 3.19, 95% CI 0.13, 76.42, P value = 0.47); respiratory: 5 studies, 280 participants. RR 0.62, 95% CI 0.26 to 1.52, P value = 0.30). There was moderate-quality evidence that showed comparable analgesic efficacy across all time points both at rest and after coughing or physiotherapy (14 studies, 698 participants). There was moderate-quality evidence that showed PVB had a better minor complication profile than TEB including hypotension (8 studies, 445 participants. RR 0.16, 95% CI 0.07 to 0.38, P value < 0.0001), nausea and vomiting (6 studies, 345 participants. RR 0.48, 95% CI 0.30 to 0.75, P value = 0.001), pruritis (5 studies, 249 participants. RR 0.29, 95% CI 0.14 to 0.59, P value = 0.0005) and urinary retention (5 studies, 258 participants. RR 0.22, 95% CI 0.11 to 0.46, P value < 0.0001). There was insufficient data in chronic pain (six or 12 months). There was no difference found in and length of hospital stay (3 studies, 124 participants). We found no studies that reported costs. AUTHORS' CONCLUSIONS: Paravertebral blockade reduced the risks of developing minor complications compared to thoracic epidural blockade. Paravertebral blockade was as effective as thoracic epidural blockade in controlling acute pain. There was a lack of evidence in other outcomes. There was no difference in 30-day mortality, major complications, or length of hospital stay. There was insufficient data on chronic pain and costs. Results from this review should be interpreted with caution due to the heterogeneity of the included studies and the lack of reliable evidence. Future studies in this area need well-conducted, adequately-powered RCTs that focus not only on acute pain but also on major complications, chronic pain, length of stay and costs.

Volatile vs Total intravenous Anaesthesia for major non-cardiac surgery: a pragmatic randomised triaL (VITAL).

BACKGROUND: Improving outcomes after surgery is a major public health research priority for patients, clinicians and the NHS. The greatest burden of perioperative complications, mortality and healthcare costs lies amongst the population of patients aged over 50 years who undergo major non-cardiac surgery. The Volatile vs Total Intravenous Anaesthesia for major non-cardiac surgery (VITAL) trial specifically examines the effect of anaesthetic technique on key patient outcomes: quality of recovery after surgery (quality of recovery after anaesthesia, patient satisfaction and major post-operative complications), survival and patient safety. METHODS: A multi-centre pragmatic efficient randomised trial with health economic evaluation comparing total intravenous anaesthesia with volatile-based anaesthesia in adults (aged 50 and over) undergoing elective major non-cardiac surgery under general anaesthesia. DISCUSSION: Given the very large number of patients exposed to general anaesthesia every year, even small differences in outcome between the two techniques could result in substantial excess harm. Results from the VITAL trial will ensure patients can benefit from the very safest anaesthesia care, promoting an early return home, reducing healthcare costs and maximising the health benefits of surgical treatments. TRIAL REGISTRATION: ISRCTN62903453. September 09, 2021.

Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial.

OBJECTIVE: To evaluate whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with post-covid-19 condition (long covid). DESIGN: Pragmatic, multicentre, parallel group, superiority randomised controlled trial. SETTING: England and Wales, with home based interventions delivered remotely online from a single trial hub. PARTICIPANTS: 585 adults (26-86 years) discharged from NHS hospitals at least three months previously after covid-19 and with ongoing physical and/or mental health sequelae (post-covid-19 condition), randomised (1:1.03) to receive the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) intervention (n=298) or usual care (n=287). INTERVENTIONS: Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. MAIN OUTCOME MEASURES: The primary outcome was health related quality of life using the patient reported outcomes measurement information system (PROMIS) preference (PROPr) score at three months. Secondary outcomes, measured at three, six, and 12 months, included PROMIS subscores (depression, fatigue, sleep disturbance, pain interference, physical function, social roles/activities, and cognitive function), severity of post-traumatic stress disorder, general health, and adverse events. RESULTS: Between January 2021 and July 2022, 39 697 people were invited to take part in the study and 725 were contacted and eligible. 585 participants were randomised. Mean age was 56 (standard deviation (SD) 12) years, 52% were female participants, mean health related quality of life PROMIS-PROPr score was 0.20 (SD 0.17), and mean time from hospital discharge was 323 (SD 144) days. Compared with usual care, the REGAIN intervention led to improvements in health related quality of life (adjusted mean difference in PROPr score 0.03 (95% confidence interval 0.01 to 0.05), P=0.02) at three months, driven predominantly by greater improvements in the PROMIS subscores for depression (1.39 (0.06 to 2.71), P=0.04), fatigue (2.50 (1.19 to 3.81), P<0.001), and pain interference (1.80 (0.50 to 3.11), P=0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P=0.02). Of 21 serious adverse events, only one was possibly related to the REGAIN intervention. In the intervention group, 141 (47%) participants fully adhered to the programme, 117 (39%) partially adhered, and 40 (13%) did not receive the intervention. CONCLUSIONS: In adults with post-covid-19 condition, an online, home based, supervised, group physical and mental health rehabilitation programme was clinically effective at improving health related quality of life at three and 12 months compared with usual care. TRIAL REGISTRATION: ISRCTN registry ISRCTN11466448.

A qualitative study exploring the lived experiences of patients living with mild, moderate and severe frailty, following hip fracture surgery and hospitalisation.

It is well recognised that hip fracture surgery is associated with a negative impact on short and long-term post-operative physical health and emotional well-being for patients. Furthermore, these patients are known to be frail with multiple co-morbidities. This study explores how frailty shapes the lived experiences of rehabilitation and recovery for patients who have undergone hip fracture surgery. Semi-structured interviews were conducted with sixteen participants, recently discharged from hospital following hip fracture surgery. Interpretative phenomenological analysis was applied to explore the lived experiences of frail patients and ascertain important themes. Patient experiences were captured in seven overarching themes: 1) the hospital as a place of "safety", 2) placing trust in others, 3) the slow recovery journey impeded by attitude and support, 4) maintaining autonomy and dignity whilst feeling vulnerable, 5) seeking a new normal, 6) loneliness and social isolation and 7) the ageing body. Based on our study findings, we have been able to suggest a number of opportunities to improve support for frailer patients in finding a new routine to their everyday lives, these include on-going physical and psychological support, information and education and a robust pathway for transition of care into the community. A conceptual thematic diagram is presented which helps to understand the experience and the complex needs of frail older people undergoing hip fracture surgery.